From the AGA Journals

Proinflammatory diet linked to colorectal cancer testing positive for Fusobacterium nucleatum

 

Key clinical point: A proinflammatory diet was associated with a significantly increased risk for colorectal cancer testing positive for Fusobacterium nucleatum.

Major finding: Dietary scores in the highest inflammatory tertile correlated with significantly increased risk (HR, 1.63; P = .03).

Study details: Longitudinal study of self-reported dietary patterns and cancers among 124,433 individuals with 28 years of follow-up.

Disclosures: Funders included the National Institutes of Health, Dana Farber Harvard Cancer, Project P. Fund for Colorectal Cancer Research, Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, the Entertainment Industry Foundation, and American Association for Cancer Research, National Natural Science Foundation of China, Chinese Scholarship Council, Huazhong University of Science and Technology, and others. Dr. Liu had no disclosures. One coinvestigator disclosed ties to Genentech/Roche, Lilly, Sanofi, Bayer, and several other biomedical companies.

Source: Liu L et al. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j.cgh.2018.04.030.

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Study shows interplay of diet and microbiome

The underlying reasons colorectal cancer (CRC) develops are unknown, but they likely include a complex interaction between genetics and environmental exposures. Recent studies have highlighted important links between diet, the intestinal microbiota, and CRC development and progression.

Dr. Rajesh R. Shah

Liu et al. used the Nurses’ Health Study and Health Professionals Follow-Up Study cohorts to extend our understanding of the relationship between diet, the intestinal microbiota, and CRC. They utilized validated food frequency questionnaires obtained every 4 years and formalin-fixed paraffin embedded CRC tissue samples collected from 951 individuals. They calculated an empiric dietary inflammatory pattern (EDIP) score, which correlates components of the diet with plasma inflammatory markers. After adjusting for confounders, they found high EDIP scores were significantly associated with Fusobacterium nucleatum–positive CRC, but not with F. nucleatum–negative CRC. In addition, they demonstrated this association was stronger for proximal compared with distal CRC. Their findings suggest an inflammatory diet may interact with the intestinal microbiota to promote the development of CRC and they provide a preliminary recommendation to minimize intake of potentially harmful foods (i.e., red meat, processed meat, refined grains, etc.). Despite the intriguing results, the authors do recognize limitations including the small number of cases with F. nucleatum present (n = 115) and the homogeneous cohort (90% non-Hispanic whites), which may limit generalizability.

As clinicians, we should continue strongly advocating for CRC screening and, based on these findings, may consider dietary recommendations to reduce intake of potentially harmful foods. Further research will be needed to confirm these findings in additional cohorts and to clarify the molecular interactions between dietary components, intestinal microbiota, and development of CRC.

Rajesh R. Shah, MD, is assistant professor of gastroenterology, department of internal medicine, Baylor College of Medicine, Houston. He has no conflicts of interest.


 

FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY

Diets promoting colonic inflammation were associated with a greater risk of colorectal carcinomas containing Fusobacterium nucleatum bacteria, according to a report in the October issue of Clinical Gastroenterology and Hepatology.

Courtesy American Gastroenterological Association

Proinflammatory diets were not linked to heightened risk for colon cancers without these bacteria, reported Li Liu, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston. “These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis,” they wrote. “Nutritional interventions might be used in precision medicine and cancer prevention.”

Intestinal inflammation, a risk factor for colorectal cancer, is associated with high levels of circulating interleukin 6, C-reactive protein, and tumor necrosis factor–receptor superfamily member 1B. Colonic inflammation impairs the mucosal barrier and alters immune cell responses, which affects the composition of colonic microbiota. Among these, F. nucleatum is known to potentiate colorectal tumors and is associated with proximal tumor location, other tumor features, and cancer progression and chemoresistance.

For the study, the investigators examined self-reported data from more than 124,000 individuals followed for 28 years as part of the Nurses’ Health Study and the Health Professionals Follow-Up Study. They calculated average dietary patterns based on the empiric dietary inflammatory pattern (EDIP) score, which sums weighted intake scores for 18 foods (such as red and processed meat, coffee, tea, and leafy green or dark yellow vegetables) that are known to affect plasma levels of interleukin 6, C-reactive protein, tumor necrosis factor–receptor superfamily member 1B, and tumor necrosis factor alpha–receptor 2. A higher EDIP score denotes a more inflammatory diet.

During the 28-year follow-up period, 951 individuals developed colorectal carcinomas that were tested with a polymerase chain reaction assay for F. nucleatum DNA. A total of 115 tumors tested positive for F. nucleatum. After the researchers controlled for potential confounders, individuals whose EDIP scores were in the highest tertile were significantly more likely to develop F. nucleatum–positive colorectal cancer than were those who scored in the lowest tertile (adjusted hazard ratio, 1.63; 95% confidence interval, 1.03 to 2.58; P = .03). This differential association “appeared to be stronger in proximal colon cancer than in distal colon and rectal cancer,” the researchers said.

More than 90% of individuals in this study were non-Hispanic white, the researchers noted. Tumor tissue was not available from all cases of colorectal cancer and a fairly small number of cases tested positive for tumor F. nucleatum. Nonetheless, the findings suggest that an inflammatory diet could help amplify gut microbiota involved in tumorigenesis, they said. Pending confirmatory studies, they recommended an anti-inflammatory diet with high intake of green leafy vegetables, dark yellow vegetables, coffee, and tea, and with low intake of red meat, processed meat, refined grain, and sugary beverages. They also recommended studying whether F. nucleatum tumor or stool tests could help personalize dietary interventions.

Funders included the National Institutes of Health, Dana Farber Harvard Cancer, Project P. Fund for Colorectal Cancer Research, Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, the Entertainment Industry Foundation, and American Association for Cancer Research, National Natural Science Foundation of China, Chinese Scholarship Council, Huazhong University of Science and Technology, and others. Dr. Liu had no disclosures. One coinvestigator disclosed ties to Genentech/Roche, Lilly, Sanofi, Bayer, and several other biomedical companies.

SOURCE: Liu L et al. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j.cgh.2018.04.030.

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